Infectious Disease
Dupilumab reduces severe asthma exacerbations and improves lung function in children
Source / information
Source:
Bacharian LB et al. Latest news: Clinical study results in pulmonary medicine. Presented at: American Thoracic Society International Conference; 14.-19. May 2021 (virtual meeting).
Disclosure:
Bacharian reports that he has received speaking fees from AstraZeneca, GlaxoSmithKline, Regeneron, and Sanofi; served on the data security supervisory board at Cystic Fibrosis Foundation and DBV Technologies; and received research support from NIH, Sanofi, and Vectura.
ADD SUBJECT TO EMAIL ALARMS
Receive an email when new articles are published
Please enter your email address to receive an email when new articles are published . “data-action =” subscribe “> subscribe
We could not process your request. Please try again later. If you continue to have this problem, please contact [email protected].
Back to Healio
Dupilumab significantly reduced asthma exacerbations and improved lung function within 2 weeks in children 6-11 years of age with uncontrolled moderate to severe asthma with signs of type 2 inflammation.
Treatment with dupilumab (Dupixent, Sanofi / Regeneron) also led to a significant improvement in asthma symptom control and a reduction in fractionated exhaled nitric oxide (FeNO), according to the American Thoracic Society International Conference.
Source: Adobe Stock.
“Uncontrolled asthma in children remains a major challenge and we still have many children who compromise their quality of life and activities because of uncontrolled asthma. Over the past two decades we have been fortunate enough to develop biological therapies for asthma that have helped improve the lives of many asthmatics significantly, and over time we have been able to begin studying these therapies in younger patients ” Leonard B. Bacharian, MD, Professor of pediatrics at Vanderbilt University’s Monroe Carroll Jr. Children’s Hospital, Healio said. “Now we have a great opportunity to study the effectiveness of any of these therapies in children 6 years and older to see if the effects of this therapy are effective in younger children and school age children, as has been shown in adolescents and adults. “
The LIBERTY ASTHMA VOYAGE randomized, double-blind, placebo-controlled phase 3 study evaluated the efficacy and safety of dupilumab, a fully human monoclonal antibody that inhibits the signaling of the proteins interleukin-4 and interleukin-13. The study enrolled 408 children aged 6 to 11 years with uncontrolled moderate to severe uncontrolled asthma who were treated with a medium-dose inhaled corticosteroid (ICS) with a second controller or a high-dose ICS with or without a second controller. More than 90% of the children in the study had at least one simultaneous type 2 inflammatory disease, including atopic dermatitis and eosinophilic esophagitis.
Children were randomly assigned to receive dupilumab 100 mg or 200 mg subcutaneous dupilumab based on baseline body weight for 52 weeks or placebo every 2 weeks for 52 weeks. The primary analysis assessed two pre-determined populations with evidence of type 2 inflammation: patients with baseline blood eosinophils > 300 cells / µL (n = 259) and patients with the type 2 phenotype of inflammatory asthma (FeNO) > 20 ppb or blood eosinophils > 150 cells / µl; n = 350).
Healio previously reported on the key results of the LIBERTY ASTHMA VOYAGE study announced in October 2020.
“Dupilumab reduced the annualized rate of severe exacerbations in all efficacy populations,” said Bacharian during the presentation.
The primary endpoint was the annualized exacerbation rate in severe asthma, which was reduced by 65% (P <0.0001) in children with blood eosinophils > 300 cells / µL and 59% (P <0.0001) in patients with inflammatory phenotype type 2 after 52 weeks compared to placebo (0.24 events per year and 0.31 events per year with dupilumab versus 0.67 and 0.75 with placebo). The researchers reported similar results in other populations identified by individual markers for type 2 inflammation (61% reduction in patients with blood eosinophils > 150 cells / µl and 62% reduction in those with FeNO > 20 ppb) and in the intention-to-treat population (54% reduction) according to the presentation.
Dupilumab also resulted in rapid and sustained improvements in lung function, with improvement seen as early as 2 weeks and lasting up to 52 weeks. After 12 weeks, children given dupilumab improved their lung function by 5.32 and 5.21 percentage points compared to placebo (P = 0.0036 and P = 0.0009, respectively), according to a company press release. The researchers observed similar results in patients with blood eosinophils > 300 cells / µL and those with the inflammatory phenotype type 2.
In addition, dupilumab also resulted in improved asthma control. Compared to placebo, children who received dupilumab showed improved asthma control in the asthma control questionnaire 7 by an additional 0.46 and 0.33 points after 24 weeks (P. < .0001).
“After starting treatment in the dupilumab and placebo groups, as well as in the primary efficacy populations, there were rapid improvements in asthma control scores. Although clinically meaningful improvements were noted in both treatment groups, there was a clear difference between patients on dupilumab and patients on placebo at the end of the treatment period, ”said Bacharian during the presentation.
The presented results also showed a significant reduction in mean FeNO levels below the threshold for type 2 inflammation. Children given dupilumab showed mean improvements in FeNO levels of -20.59 ppb and -17.84 ppb compared to placebo from baseline up to 12 weeks (P <0.0001 for both).
The safety results were generally consistent with the known safety profile of dupilumab in subjects 12 years of age and older with uncontrolled moderate to severe asthma. Treatment-related adverse events were reported in 83% of children treated with dupilumab and 80% with placebo. The most common adverse events in the dupilumab group were injection site reactions, viral upper respiratory infections and eosinophilia.
“In children 6 years of age, the addition of biological dupilumab in children with moderate to severe uncontrolled asthma, and particularly in children with type 2 inflammatory patterns, results in a clinically meaningful reduction in the risk of severe exacerbations that require oral steroids, ameliorates this FEV1 significantly and improves asthma control, ”Bacharian told Healio. “This should then translate into improved life experiences for these children.”
An open-label extension of the LIBERTY ASTHMA VOYAGE study is currently ongoing and is expected to be completed later this year, Bacharian told Healio.
An FDA decision on children with moderate to severe asthma is expected by October, according to the press release.
References:
ADD SUBJECT TO EMAIL ALARMS
Receive an email when new articles are published
Please enter your email address to receive an email when new articles are published . “data-action =” subscribe “> subscribe
We could not process your request. Please try again later. If you continue to have this problem, please contact [email protected].
Back to Healio
